Patrick T. Roughneen

Impaired specific cell-mediated immunity in experimental biliary obstruction and its reversibility by internal biliary drainage.

Little is known of the effect of cholestasis on host immunity. This study evaluates lymphocytic responsiveness to PHA and LPS mitogen and to allogeneic F344 antigen in Sprague-Dawley rats 21 days following bile duct ligation and 31 days following relief of jaundice by internal biliary drainage. Serum bilirubin level was significantly elevated in the bile duct ligated animals at Day 21 (P less than 0.001) and thereafter returned to preoperative levels following internal biliary drainage. Results demonstrate depressed responsiveness to PHA (P less than 0.001) and allogeneic F344 antigen in vivo (P less than 0.04) and in vitro (P less than 0.02) in bile duct ligated animals as compared to sham, sham pair-fed, and normal control rats. The observed deficiency in responsiveness to T-cell-dependent mitogen and antigen cannot be explained on the basis of complicating nutritional, renal, or infective factors. Subsequent internal biliary drainage results in some improvement in T-cell responsiveness in the bile duct ligated group although recovery is not complete. B-Lymphocytic response to LPS mitogen is not affected by bile duct ligation. We conclude that cholestasis subsequent to extrahepatic biliary obstruction per se results in impairment of cell-mediated immunity in vivo. This impairment is partly reversible by internal biliary drainage. In vitro B-cell function does not appear to be affected in this model. Further study of impaired cell-mediated immunity in extrahepatic biliary obstruction will improve our understanding of the immunological status of patients with obstructive jaundice and cholestatic liver diseases.

Impaired nonspecific cellular immunity in experimental cholestasis

The abilities of polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM), to demonstrate chemotaxis, phagocytosis, and superoxide release after bile duct ligation in the rat were investigated to determine the effect of cholestasis on nonspecific cellular immune mechanisms. Chemotactic response to C5a and FMLP, phagocytosis of 14C labeled Staphylococcus aureus, and zymosan-induced superoxide release were evaluated 21 days after bile duct ligation (BDL), sham operation, or in normal controls. Serum total bilirubin level was elevated after BDL (p less than 0.01). Chemotactic ability was similar to each group. PMN phagocytic uptake of 14C labeled Staphylococcus aureus was depressed in BDL (p less than 0.05). BDL rats exhibited impaired PAM phagocytic indices and improved PMN superoxide release (p less than 0.03). PAM superoxide release was similar in each study group. Alterations in phagocytic function with cholestasis are important deficits in nonspecific cellular immunity that may contribute to the high incidence of infective complications associated with obstructive jaundice.

Postoperative alterations in interorgan glutamine exchange in enterectomized dogs

The effect of enterectomy on postoperative visceral organ glutamine exchange was studied in order to gain further understanding of the role of the intestinal tract in the altered glutamine metabolism that occurs following catabolic illness. In addition to studying glutamine, which transports 1/3 of whole blood amino acid nitrogen, we determined the fluxes of glutamate and alanine across the gastrointestinal tract, liver, and kidneys in 18 postoperative dogs. Arterial glutamine and glutamate were significantly higher in enterectomized animals than in controls. With enterectomy the gut became an organ of glutamine balance while in control dogs the GI tract consumed glutamine (0.11 +/- 0.04 vs 1.67 +/- 0.14 mumole/kg X min, P less than 0.001). The gut switched from an organ of glutamate release to one of net glutamate uptake following enterectomy and intestinal alanine release simultaneously fell by 50%. Simultaneously, the liver reduced its uptake of alanine and became an organ of glutamine release. Renal glutamine consumption was also diminished in enterectomy animals. The interorgan exchange of glutamine and other amino acids is altered by enterectomy. The increase in circulating glutamine levels in enterectomized animals suggests that the accelerated intestinal glutamine consumption that characterizes catabolic illnesses contributes to the low glutamine levels in these stress states. In addition, it becomes apparent that the gut is an important supplier of alanine to the liver, which supports gluconeogenesis. Metabolic adaptation and cooperation between organs is essential during organ absence or dysfunction if the organism is to survive critical illness.

Modified Konno-Rastan Procedure for Subaortic Stenosis: Indications, Operative Techniques, and Results

BACKGROUND Diffuse or unresectable subaortic stenosis (SAS) necessitates an aggressive surgical approach for the elimination of left ventricular outflow tract obstruction. In this article we report our experience with the modified Konno-Rastan procedure, with inherent preservation of the native aortic valve and annulus, in the treatment of diffuse or unresectable SAS. METHODS Sixteen children (age range, 21 months to 18 years) underwent the modified Konno-Rastan procedure through either a transventricular (n = 12) or a transatrial approach (n = 4) to the conal septum. Indications for operation were recurrent SAS (n = 3), hypertrophic obstructive cardiomyopathy (n = 3), tunnel stenosis (n = 2), SAS related to a canal (n = 3), and SAS after ventricular septal defect closure (n = 5). Eleven patients had undergone previous procedures and 5 underwent the modified Konno-Rastan procedure as their primary operation. RESULTS The mean preoperative left ventricular outflow tract gradient of 50 +/- 17 mm Hg was reduced to 3 +/- 7 mm Hg (p < 0.001) after surgical repair. Postoperative complications included sternal infection (n = 1), heart block (n = 2), mediastinal bleeding (n = 1), and renal and cerebral ischemia (n = 1). There was 1 late postoperative death caused by pneumonia 2 years after operation (6.2% mortality rate). The mean follow-up period was 62 +/- 39 months and all patients had complete relief of preoperative symptoms and were in New York Heart Association class I. One patient underwent a successful redo modified Konno-Rastan procedure 7 years after the first operation for residual left ventricular outflow tract obstruction immediately below the aortic valve. One patient is awaiting reoperation for aortic incompetence unrelated to conal enlargement 1.5 years after the first procedure. CONCLUSIONS The modified Konno-Rastan procedure represents an excellent therapy for diffuse or unresectable SAS in patients with a normal aortic valve. In addition, it produces excellent results in a limited number of patients with hypertrophic obstructive cardiomyopathy, in whom the Morrow procedure traditionally has been performed. Although it usually is performed through a transventricular approach, the modified Konno-Rastan procedure also can be performed through a transatrial approach; this is particularly useful in patients who have had previous ventricular septal defect closure associated with SAS occurring proximal to the prosthetic patch.

The pericardial membrane pulmonary monocusp: Surgical technique and early results

Long‐term pulmonary insufficiency resulting from simple transannular patching of the right ventricle outflow tract will ultimately lead to deterioration in right ventricular function. Previously, monocusps constructed from xenografts, homografts, fascia lata, and autologous pulmonary artery wall have been utilized to minimize pulmonary regurgitation and its deleterious effect on right ventricular function. However, these tend to degenerate in the long term, necessitating reoperation. To circumvent this problem we have used a monocusp constructed from 0.1‐mm polytetrafluorethylene (PTFE, pericardial membrane) clinically demonstrated to be resistant to issue ingrowth and degeneration. Seven children (5 tetralogy of Fallot, 2 pulmonary stenosis) who required division of a small pulmonary an‐nulus underwent monocusp construction with 0.1‐mm PTFE. Three patients had previous corrective surgery. One of these patients had a bovine pericardial monocusp placed 8 years previously, which degenerated. Of the remaining two patients, one had a pulmonary valvo‐tomy as a neonate, the other repair of tetralogy of Fallot with a transannular patch. At a mean (± standard deviation) follow up to 17 ± 5.8 months all patients are alive and are New York Heart Association (NYHA) Class I. Echocardiography demonstrates mild pulmonary insufficiency (PI) in 2 patients, mild to moderate PI in 4, and moderate to severe PI in 1. The presence of a pericardial membrane monocusp in the pulmonary position may, in the long term, prevent the deleterious effects of transannular patching on right ventricular dysfunction and be more resistant to degenerative changes characteristic of monocusps constructed of native pericardium or allogeneic tissue.

Management of Arch Hypoplasia After Successful Coarctation Repair

BACKGROUND Pronounced arch obstruction can be seen after a well-repaired coarctation, and this probably results from the failure of a somewhat hypoplastic arch to grow or from clamp injury at the time of the initial repair, or from both causes. Because of mediastinal adhesions and minimal collateral circulation, use of extraanatomic bypass grafts appears to be the preferred approach. METHODS Six children or young adults presented with arch obstruction over a 3-year period. Their mean age was 13.5 +/- 4 years, and the mean interval from the time of the initial repair was 10 +/- 4 years. The mean age of the patients at the time of the initial repair was 3.2 +/- 5 years. Symptoms included exertional headache and chest pain. The mean systolic gradients, as shown by echocardiography and cardiac catheterization, were 34 +/- 7 mm Hg and 33 +/- 6 mm Hg, respectively. Repair was accomplished through a midsternotomy using a polytetrafluoroethylene patch placed in the concavity of the arch, which extended from the ascending to the descending aorta. Dissection was kept close to the aorta and arch to minimize injury to the phrenic and recurrent laryngeal nerves. Cardiopulmonary bypass and moderate hypothermia (25 degrees to 27 degrees C bladder temperature) without circulatory arrest were used. RESULTS All patients were discharged home 4 to 20 days postoperatively (mean, 7 +/- 6 days). All patients were found to be normotensive at a mean follow-up of 1.3 +/- 1 years. Postoperative echocardiograms, which were obtained in all patients, revealed no residual gradients. Exercise blood pressure was evaluated in 2 patients and found to be normal. CONCLUSIONS Transsternal arch enlargement using cardiopulmonary bypass and moderate hypothermia without circulatory arrest is an attractive and safe approach for the treatment of arch obstruction after coarctation repair. Unlike the use of extraanatomic bypass grafts, it allows complete relief of the obstruction, unhampered aortic growth, the minimal use of foreign material, and a repair that is protected deep within the mediastinal space.

Experimental Evidence of Cerebral Injury from Profound Hypothermia During Cardiopulmonary Bypass

Abstract. Choreoathetosis, seizures, and impaired mental development continue to occur in children undergoing cardiopulmonary bypass (CPB) and profound hypothermia with or without circulatory arrest. Although there is some evidence that the hypothermia itself may be causing these neurologic problems, skepticism remains because of lack of evidence from experimental studies simulating the clinical setting. In this experimental study, we examined the effect of profound and moderate hypothermia on the brain while maintaining normal flow rates during CPB. Ten adult mongrel dogs equally divided into two groups were anesthetized and subjected to CPB and varying levels of hypothermia (group 1, ≤15°C; group 2, ≤32°C). Both groups were kept at the desired temperature for 1 hour prior to rewarming and discontinuation of CPB. The dogs were euthanized 4–6 weeks later and neuropathologic studies were performed. The mean CPB flow rates during cooling and at the desired rectal temperature were comparable in both groups: group 1, 108 ± 10 ml/kg/min versus 106 ± 7 ml/kg/min in group 2 (p= NS) and 95 ± 12 ml/kg/min in group 1 versus 101 ± 5 ml/kg/min in group 2 (p= NS). Because of the difference in temperature between the two groups, the mean cooling time (onset of CPB to desired rectal temperature) was longer in group 1 (70 ± 14 minutes) than in group 2 (28 ± 11 minutes, p= 0.007). Hence, the total mean CPB time was also longer in group 1 (198 ± 25 minutes) than in group 2 (143 ± 13 minutes, p= 0.002). The lowest mean blood and rectal temperature achieved in group 1 were 11 ± .9°C and 12 ± 1°C versus 29 ± .4°C (p < 0.001) and 30 ± .6°C (p= 0.001), respectively, in group 2 (p= 0.001). Neuronal loss and degeneration was noted in all dogs in group 1 ranging from 2 to 8 cells per 1000 cells counted compared to none in group 2 (p= 0.05). These lesions occurred in both the basal ganglia and the cortex, although they were more marked in the caudate when compared to the cortex and cerebellum. Both in the cortex and in the caudate, neuronal loss was more marked around the capillaries. We conclude that the use of profound hypothermia of ≤15°C and maintenance of normal flow rates during cooling at this temperature for 1 hour produces neuronal loss and degeneration in the brain. These lesions being more marked around capillaries points to the vulnerability of the neurons, probably because of their high lipid content to injury from the cold perfusate.

Simultaneous repair of pectus excavatum and congenital heart disease

Most repair of heart lesions and pectus deformity has been performed in adult patients using long incisions, sternal splits, excision of deformed cartilages, and sternal turnover operations that could result in poor cosmesis and chest growth in children because of sternal devascularization. We performed simultaneous pectus repair and atrial septal defect closure in 2 children using a short longitudinal incision and avoiding a transverse or longitudinal sternal split. After extraperichondrial excision of the deformed cartilages and mobilization of the sternum from the neurovascular bundles, a transverse wedge of sternum was removed at the level of the third cartilages, allowing cephalad retraction of the sternum and providing excellent exposure for the intracardiac operation. The cosmetic appearance remains excellent in both patients at 1 and 4 years postoperatively.

Extended end-to-end repair and enlargement of the entire arch in complex coarctation

BACKGROUND Treatment of hypoplasia of the entire arch in coarctation is a surgical challenge. The current approaches have technical difficulties, high recurrence rates, and increased morbidity and mortality. METHODS Over a 14-month period, a combined extended end-to-end repair with patch enlargement of the concavity of the entire arch was performed in 6 neonates and 1 infant. Through a midsternotomy and using cardiopulmonary bypass and hypothermia, extended end-to-end repair was performed initially leaving the proximal anastomosis open. The enlarging polytetrafluoroethylene patch was then sutured starting at the incised descending aorta distal to the extended end-to-end repair and continued retrogradely through the transverse arch to the ascending aorta proximal to the aortic cannulation site. One neonate had a patent ductus arteriosus and another had ventricular septal defect closure. One neonate had arterial switch and 3 had Norwood-type procedures performed with the enlarging patch extended to the pulmonary artery anastomosis. The remaining infant had arch enlargement performed after an arterial switch procedure and extended end-to-end repair. RESULTS All patients did well and showed no residual gradient up to 1 year follow-up. Two patients successfully had bidirectional Glenn shunt at 9 months of age, and one had closure of residual arterial septal defect at 8 months of age. CONCLUSION The combined extended end-to-end repair and arch enlargement procedure should minimize recurrence rates because of a tension-free enlargement of the entire aortic arch and elimination of the coarctation ridge and ductile tissues. Combined with the arterial switch and Norwood-type procedures, the approach results in a large neoaorta.

Inflammatory cell function in young rodents with experimental cholestasis: investigations of functional deficits, their etiology, and their reversibility.

Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)